title: Antiretroviral therapy outcomes in HIV-infected children after adjusting protease inhibitor dosing during tuberculosis treatment.
abstract: BACKGROUND
  Modification of ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy is required for HIV-infected children co-treated for tuberculosis (TB). We aimed to determine virologic and toxicity outcomes among TB/HIV co-treated children with the following modifications to their antiretroviral therapy (ART): (1) super-boosted LPV/r, (2) double-dose LPV/r or (3) ritonavir.
  
  
  RESULTS
  A medical record review was conducted at two clinical sites in Johannesburg, South Africa. The records of children 6-24 months of age initiating LPV/r-based therapy were reviewed. Children co-treated for TB were categorized based on the modifications made to their ART regimen and were compared to children of the same age at each site not treated for TB. Included are 526 children, 294 (56%) co-treated for TB. All co-treated children had more severe HIV disease, including lower CD4 percents and worse growth indicators, than comparisons. Children in the super-boosted group (n = 156) were as likely to be virally suppressed (<400 copies/ml) at 6 months as comparisons (69.2% vs. 74.8%, p = 0.36). Children in the double-dose (n = 47) and ritonavir groups (n = 91) were significantly less likely to be virally suppressed at 6 months (53.1% and 49.3%) than comparisons (74.8% and 82.1%; p = 0.02 and p<0.0001, respectively). At 12 months only children in the ritonavir group still had lower rates of virological suppression relative to comparisons (63.9% vs 83.3% p<0.05). Grade 1 or greater ALT elevations were more common in the super-boosted (75%) than double-dose (54.6%) or ritonavir (33.9%) groups (p = 0.09 and p<0.0001) but grade 3/4 elevations were observed in 3 (13.6%) of the super-boosted, 7 (15.9%) of the double-dose and 5 (8.9%) of the ritonavir group (p = 0.81 and p = 0.29).
  
  
  CONCLUSIONS
  Good short-term virologic outcomes were achieved in children co-treated for TB and HIV who received super-boosted LPV/r. Treatment limiting toxicity was rare. Strategies for increased dosing of LPV/r with TB treatment warrant further investigation.
authors.affiliation: Gertrude H. Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: Cordula
authors.initials: C
authors.lastname: Frohoff
authors.forename: Magendhree
authors.initials: M
authors.lastname: Moodley
authors.forename: Lee
authors.initials: L
authors.lastname: Fairlie
authors.forename: Ashraf
authors.initials: A
authors.lastname: Coovadia
authors.forename: Harry
authors.initials: H
authors.lastname: Moultrie
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
authors.forename: Tammy
authors.initials: T
authors.lastname: Meyers
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D054796:Drug Dosage Calculations; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D008297:Male; D019338:Polypharmacy; D012189:Retrospective Studies; D020379:Risk Adjustment; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D004338:Drug Combinations; D017320:HIV Protease Inhibitors